fig5

Figure 5. The proposed HTRA1-MMP9 axis in wet AMD. The ARMS2-HTRA1 risk haplotype increases expression of HTRA1, heightening the degradation of ECM constituents. HTRA1-mediated cleavage of the ECM protein fibronectin generates fibronectin fragments, which stimulate MMP9 expression. Positive feedback between MMP9 and VEGF promotes CNV and leads to wet AMD. AMD: age-related macular degeneration; ECM: extracellular membrane; VEGF: vascular endothelial growth factor; CNV: choroidal neovascularization